Method of fabricating flexible artificial retina devices

ABSTRACT

Fabrication methods for a flexible device for retina prosthesis are described. Layered structures including an array of pixel units may be formed over a substrate. Each pixel unit may comprise a processing circuitry, a micro electrode and a photo sensor. A first set of biocompatible layers may be formed over the layered structures. The substrate may be thinned down to a controlled thickness of the substrate to allow bending of the substrate to the curvature of a retina. A second set of biocompatible layers may be formed over the thinned substrate. The second set of biocompatible layers may be in contact with the first set of biocompatible layers to form a biocompatible seal wrapping around the device to allow long-term contact of the device with retina tissues. Micro electrodes of the pixel units may be exposed through the openings of these biocompatible layers.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation in part of, and claims thebenefit of U.S. patent application Ser. No. 13/102,596, filed on May 6,2011 entitled “RETINA STIMULATION APPARATUS AND MANUFACTURING METHODTHEREOF”, which claims the benefit of Provisional Patent Application No.61/407,229, filed on Oct. 27, 2010, entitled “Retina Prosthesis and theFabrication Methods of Such”, both of which are hereby incorporated byreference in its entirety into this application.

FIELD OF INVENTION

The present invention relates generally to micro devices, and moreparticularly to flexible integrated circuit devices capable ofstimulating neural cells.

BACKGROUND

Age-related macular disease (AMD) and the retinitis pigmentosa (RP)disease have been identified as major causes of blindness, especiallyfor senior people worldwide. Retinal prosthesis device offers possiblerestoration of part of the vision to the blindness. Typically, thedevice includes micro electrodes requiring separate wiring implant tocontrol each micro electrode. However, field of view provided by suchdevices, which depends on the number of micro electrodes and pitch ofmicro electrodes included in the device, may be severely limited becauseof size limitation on the wiring implant.

Furthermore, the image resolution of a retina prosthesis device may berelated to density of micro electrodes in the device. Conventionaldevices for retina prosthesis may include driving circuit chips separatefrom electrode or image sensor chips implanted to retina tissues. Thus,the required number of electrical interconnections between the microelectrode chips and the driving circuit chips can increase significantlyand impose unnecessary ceilings on achievable number of pixels.

In addition, existing retina prosthesis devices may be based on microelectrodes made of planner chips not conforming to non-planar shapes ofretina tissues. As a result, additional interferences among the microelectrodes may occur because of the mismatch in shapes to further limitpossible image resolution of the device.

Thus, traditional retina prosthesis devices are inherently limited toprovide levels of image resolutions, field of views or other visualcharacteristics to achieve levels close to a real retina to helppatients recover from impaired vision capabilities.

SUMMARY OF THE DESCRIPTION

In one embodiment, a flexible integrated device can provide highresolution of electrical excitations (e.g. down to individual retinacell level) over at least one mm (millimeter) to several mm of retinaarea corresponding to a few degrees to a few tens of degrees field ofview for retina prosthesis. The flexible integrated device may becapable of tuning and calibration for adjusting excitation to targetretinal neurons. In one embodiment, the flexible integrated device maybe implanted using either an epi-retinal (e.g. from the front side ofretina facing the incoming light or on the retina) approach or asub-retinal (e.g. behind the retina) approach.

In another embodiment, a single flexible CMOS (complementarymetal-oxide-semiconductor) chip can integrate an array of pixel units.Each pixel may comprise a micro electrode, photo sensor, signalprocessor and driver circuitry. The flexible chip can be fabricated thinenough to conform to the shape of a retina. For example, the flexiblechip about 3 mm in diameter may be bendable to about 90 μm (micro meter)from the center of the chip to the edge of the chip to form a twodimensional curved surface of a quasi-spherical shape similar to that ofa contact lens.

In another embodiment, a flexible integrated device may include a mosaicof sub-modules divided via boundaries. Device material except someconducting lines (e.g. metal lines) between these sub-modules may beremoved from the boundaries to increase moldability (e.g. flexibility toconform to different shapes) of the device. In some embodiments, theflexible integrated device may be perforated (e.g. with perforationholes) to maintain some fluidic flow across the device. Optionally oralternatively, the flexible integrated device may include a thinsubstrate to allow a portion of light to penetrate through the backsideof the chip to the integrated photo sensors, and applicable inepi-retinal prosthesis.

In another embodiment, a flexible integrated device may includeelectrodes fitted with local return paths (or “guard ring”) to confineand shorten the total distance of electric flows from the electrodes. Asa result, the amount of electricity lost in transit of the electricflows can be lowered to prevent unwanted stimulation of neural cellsfarther away from the target neuron cells, such as the bipolar cells organglion cells in the sub-retina case. The surfaces of electrodes may bepositioned in three dimensions manner with multiple electrode heightsfrom the substrate of the device to differentially stimulate differentlayers of neuron cells, such as strata of ON and OFF cells.

In another embodiment, a flexible integrated device may include on-chipsignal processing circuitry capable of generating appropriate stimuluswaveforms for a pixel unit by taking inputs from multiple pixel units,such as nearby neighboring pixel units. The flexible integrated devicemay include electrical sensing circuitry capable of identifying thespecific types of target neural cells interfacing to each pixel unitthrough the receptive field and firing patterns from the target neuralcells (e.g. located close to the pixel unit).

In another embodiment, a provision system including a flexibleintegrated retina chip implanted to a user as retina prosthesis mayallow fine tuning of the chip via external commands. For example, eachpixel unit in the chip may include specific receivers and/or circuitryfor receiving optical and/or wireless communication signals for theexternal commands to select and/or configure portions of the chipaccording to the user's visual perception. The provision system mayinclude a remote control to issue the external commands optically orwirelessly.

In another embodiment, a fabrication method for a flexible device havingan array of pixel units for retina prosthesis may comprise forminglayered structures including the array of pixel units over a substrate,each pixel unit comprising a processing circuitry, an electrode and aphoto sensor. A first set of biocompatible layers may be formed over thelayered structures. In one embodiment, the substrate may be thinned downto a controlled thickness of the substrate to allow bending of thesubstrate to the curvature of a retina. A second set of biocompatiblelayers may be formed over the thinned substrate. In some embodiments,the second biocompatible layer may be in contact with the firstbiocompatible layer to form a sealed biocompatible layers wrapping thedevice to allow long-term contact of the device with retina tissues.Micro electrodes of the pixel units may be exposed through the openingsof these biocompatible layers.

In another embodiment, a fabrication method for a retina stimulationdevice may comprise forming a layered structure over a substrate havinga plurality of photo sensors, a plurality of micro electrodes and aplurality of processing circuitry. The micro electrodes may be exposedover openings on a surface of the substrate. The surface including theopenings may be passivated with barrier thin films capable of protectingthe layered structure. The electrodes within the openings may be exposedthrough the barrier layer for the barrier layer to protect sidewallsaround the electrodes. The substrate may be thinned down to enablebending of the device to conform to the curvature of a retina. A polymerlayer may be formed over the barrier layer. In one embodiment, thepolymer layer may be biocompatible to allow implant of the device inliving tissues. The electrodes may be exposed through the polymer layer.

In another embodiment, a fabrication method for a device implantable fora retina may comprise forming an array of pixel units over a substrate.Each pixel unit can include a photo sensor, a micro electrode andprocessing circuitry coupled to the photo sensor and the electrode. Eachpixel unit may be coupled with neighboring pixel units in the array withconducting wires. The substrate may be thinned to a thickness to allowbending of the device to position the pixel units over a curved areaconforming to the curvature of a retina. The device may be covered withprotected layers that are biocompatible to provide bi-directionalprotection between the device and tissues associated with the retina. Aplurality of perforation holes may be opened up between the pixel unitsperpendicular to the chip surface to allow fluidic flow through thedevices via the perforation holes. The micro electrodes of the pixelunits may be exposed through the protected layers.

Other features of the present invention will be apparent from theaccompanying drawings and from the detailed description that follows.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention is illustrated by way of example and notlimitation in the figures of the accompanying drawings, in which likereferences indicate similar elements and in which:

FIGS. 1A-1B are block diagrams illustrating embodiments of integratedflexible devices for retina prosthesis;

FIGS. 2A-2B are relationship diagrams illustrating effects of flexibledevices which are curved according to one embodiment of the presentinvention.

FIG. 3 is a schematic diagram illustrating an exemplary device withperforation holes according to one embodiment of the present invention;

FIGS. 4A-4B are block diagrams illustrating cross sectional views offlexible devices in one embodiment of the present invention;

FIGS. 5A-5J are block diagrams illustrating a sequence of fabricationprocesses for flexible devices in one embodiment of the presentinvention;

FIGS. 5.1A-5.1F are block diagrams illustrating an alternative orpreferred sequence of fabrication processes for flexible devices in oneembodiment of the present invention;

FIGS. 6A-6D are block diagrams illustrating exemplary layered structuresof flexible devices for different approaches to implant retinaprosthesis;

FIGS. 7A-7B are block diagrams illustrating guard rings to providenearby return path and confine electric flows in exemplary embodimentsof the present invention;

FIG. 8 is a block diagram illustrating layered structures for flexibledevices with protruding electrodes in one embodiment of the presentinvention;

FIG. 9 is a block diagram illustrating layered structures in flexibledevices with multi-level electrodes in one embodiment of the presentinvention;

FIGS. 10A-10B are schematic diagrams illustrating exemplary signalprocessing circuitry in flexible devices according to one embodiment ofthe present invention;

FIGS. 11A-11B are block diagrams illustrating operations of configuredflexible devices in one embodiment of the present invention;

FIG. 12 is a block diagram illustrating a system to calibrate and tunethe flexible devices in one embodiment of the present invention;

FIG. 13 is a flow diagram illustrating a method to configure flexibledevices in one embodiment described herein.

DETAILED DESCRIPTION

Methods of fabricating flexible artificial retina devices are describedherein In the following description, numerous specific details are setforth to provide thorough explanation of embodiments of the presentinvention. It will be apparent, however, to one skilled in the art, thatembodiments of the present invention may be practiced without thesespecific details. In other instances, well-known components, structures,and techniques have not been shown in detail in order not to obscure theunderstanding of this description.

Reference in the specification to “one embodiment” or “an embodiment”means that a particular feature, structure, or characteristic describedin connection with the embodiment can be included in at least oneembodiment of the invention. The appearances of the phrase “in oneembodiment” in various places in the specification do not necessarilyall refer to the same embodiment.

A flexible IC (integrated circuit) device can integrate an array of“pixels” in a sing chip. Each pixel can comprise an electrode, sensors(e.g. photo sensors, electric sensors or other applicable sensors), asignal processor and/or driver circuitry. The integration can simplifywiring, fan out, multiplexing or other requirements to enable intendedfunctions of the device. Costly signal transmission, for example, via EM(electromagnetic) waves, between sensor/processing circuitry andelectrode arrays may be eliminated. Each pixel can be accessible withinthe device to allow thousands or tens of thousands of pixels in thedevice to interface with neuron cells. For example, the flexibleintegrated device may provide required density to restore a 20/80 visualacuity corresponding to about a two to four mm-sized, high density arraywith 10,000˜20,000 pixel units.

In one embodiment, flexibility of an integrated device may be based oncontrolled thickness of the device. For example, the device can be thinenough to bend ˜90 μm from the center to the edge to conform to theshape of a retina (e.g. a human eye ball). In some embodiments, thedevice may be made (e.g. according to a fabrication process) thin enoughto be bent to a radius of curvature smaller than 12 mm, about theaverage radius curvature of a human retina, still within the safetymargin of the material strength of the device.

As a device is bendable to conform to the curvature of a retina, theneuron-to-electrode distance between electrodes of the device and targetneuron cells of the retina can be reduced. Consequently, the powerrequired in each pixel to excite or stimulate the neuron cells can bereduced to enable a higher pixel density with the allowed power densitygiven and improve resolution of images perceived via the neuron cellsusing the device implanted to a patient. In certain embodiments, thedevice can meet the conformity requirements for exciting individualretinal neuron (e.g. targeting an individual neuron cell per electrode).

In one embodiment, a flexible integrated circuit (or device) for retinaprosthesis may be fabricated based on an 180 nm (nanometer) CMOStechnology using <˜30 micrometer thick Si device layer sandwichedbetween two biocompatible polymer and barrier layers (such asPolyimide/SiC, Parylene/SiC). Both biocompatible polymer (such aspolyimide, parylene, liquid-crystal polymers etc.) and barrier layer(such as SiC, TiN, DLC diamond-like carbon or diamond films etc.) may becompatible (e.g. biocompatible) with ISO (International Organization forStandardization) 10993 standards to provide bi-directional protection(e.g. to allow long-term contact) between the flexible integrated deviceand surrounding tissues when the device is implanted within the tissues.

The fabrication approach of a flexible integrated device may enableintegration of high density CMOS image sensors and signal processingcircuitry together with neuron stimulating electrode arrays on the sameflexible patch needed for medical implants. In some embodiments,semiconductor substrate may be used in the device to allow inclusion ofnecessary optical and/or electronic components for sensing opticalimages and producing electrical stimulus as a function of the sensedoptical images.

In an alternative embodiment, a flexible integrated device may beapplicable in different manners of retina implantation. For example, thedevice may be manufactured to be thin enough to allow certain portion oflight to pass through the device. Sensors and electrodes may bepositioned in the same side (or surface) or opposing sides of such atranslucent device. As a result, the device may be implanted in anepi-retina manner to stimulate retinal ganglion cells (RGC) directly viaelectrodes of the device without utilizing a retinal neural networkbefore the RGC layer. Alternatively, the device may be implanted in asub-retinal manner to stimulate the retina from the bipolar cell sidevia the electrodes, for example, to work together with the remainingneural network formed by a variety of neuron cells, such as bipolarcells, horizontal cells, amacrine cells etc.

In one embodiment, a flexible integrated device may be capable ofexciting target neuron cells or nerves according to characteristics ofthe neuron cells responding to light stimuli. For example, thecharacteristics may indicate the target neuron cells are ON type cells,OFF type cells or other types of cells. An ON type cell may respondsubstantially synchronous with onset of light stimuli. An OFF type cellmay respond substantially synchronous with offset of the light stimuli.The flexible integrated device may include processing capability togenerate stimuli from received light to properly excite the targetedneuron cells (e.g. as if the neuron cells are directly stimulated by thereceived light), for example, via special stimulation pattern (orwaveforms), time delays, ignition, suppression, or other applicablestimulation manners, etc. In one embodiment, the flexible integrateddevice may include multiple layers of electrodes (e.g. distributed in athree dimensional manner) to allow physical selection (e.g. based onproximity) of different layers of neuron cells (e.g. due to neuronconnection stratification) to communicate (or stimulate). For example,each electrode or micro electrode may be positioned to target a smallnumber (e.g. limited to be smaller than a predetermined number, such as4, 8, or other applicable number) of neuron cells without affectingother neuron cells not targeted.

A flexible integrated device may be configurable to provide customizedfunctionalities for different retina implant needs. For example, manualand/or self (automatic) calibration operations may be applied in vitro(e.g. subsequent to implantation into a patient) to identify types oftargeted neuron cells and/or adjusting sensor/electrode array parametersof the device according to actual visual perception of the receivingpatient. Processing functions may be activated or programmed (e.g.through programmable circuitry) to provide equivalent signal processingeffects, for example, to replace damaged neuron cell networks to improveimpaired vision of the receiving patient.

FIGS. 1A-1B are block diagrams illustrating embodiments of integratedflexible devices for retina prosthesis. Device 100A of FIG. 1 mayinclude a two dimensional array of pixel units. Each pixel unit mayinclude similar structures. For example, pixel unit 107 may comprise aphoto sensor 101 to receive incoming light, processing circuitry 105 toperform operations, and electrode 103 to stimulate target neuron cellsto allow perception of vision projected by the incoming light. In oneembodiment, processing circuitry 105 may include digital, analog orother applicable circuits to process sensed light from photo sensor 101for generating a stimulus or waveform, activation patterns, etc. todrive electrode 103 to stimulate the targeted neuron cells.

Alternatively, device 100B of FIG. 1B may include pixel unit 109comprising photo sensor 111, electrode 113 and circuitry 115. Electrode113 may interface with target neuron cells to deliver stimulus to and/orsense electric activities from targeted neuron cells. The stimulus maybe derived from light captured by photo sensor 111. In one embodiment,circuitry 115 may provide processing (e.g. signal processing) functionsfor receiving, processing, and/or driving electric signals. For example,electric signals may be received via sensed light from photo sensor 111or sensed electrical fields from electrode 113. Circuitry 115 may drivestimulus as electric signals via electrode 113.

The incorporation of electrical sensing circuit 115 in the retinalprosthesis chip device 100B may enable automatic or manualidentification of neuron cells through sensed receptive field (e.g.electrical field) and neuron spiking patterns in time domain. Examplesmay be functional asymmetries in ON and OFF ganglion cells of primateretina that receptive fields of ON cells is 20% larger than those of OFFcells, resulting in higher full-field sensitivity, and that On cellshave ˜20% faster response kinetics than OFF cells. A large array ofcell-sized micro electrodes conforming to the retina and capable of bothsensing and stimulating may allow selective stimulating or suppress ONand OFF retina retinal ganglion cells.

FIGS. 2A-2B are relationship diagrams illustrating effects of flexibledevices which are curved according to one embodiment of the presentinvention. Typically, image resolution and required driving power (e.g.threshold current density) of a retina prosthesis device may depend oncurvature of the device. In one embodiment, a flexible integrated devicefor retina prosthesis may include cell-pitched electrode array (e.g.each electrode is about the size of a single neuron cell) fabricated byplanar IC lithography technology. FIG. 2A shows distribution diagram200A of neuron-to-electrode distances for implementing an mm-sizedplanner electrode array chip in contact with a retina curved accordingto a human eye ball, which is roughly spherical with an average diameterof 25 mm.

As shown in distribution diagram 200A, an mm-sized planar electrodearray chip 203 in contact with the retina 201 at the chip center mayquickly separate from the retina by about 90 microns at distance 1.5 mmfrom the center toward the edge of the chip. This increase ofneuron-to-electrode distance can imply, for example, increase in thethreshold current needed for an electrode to depolarize target neurons.As shown in relationship diagram 200B of FIG. 2B, the increase in thethreshold current required can be 1˜2 orders in magnitude larger thanthat in close proximity according to curve 205. Additionally, theincrease of neuron-to-electrode distance may reduce the resolution todepolarize particular neurons since the field lines and electricalcurrents (e.g. for sending stimulus signals) from the electrodes mayspread out with distance and cover a large area to reach distantneurons. In one embodiment, a flexible integrated device of the presentinvention may be implanted without the large distance or separateimplications shown in FIGS. 2A and 2B.

FIG. 3 is a schematic diagram illustrating an exemplary device withperforation holes according to one embodiment of the present invention.Device 300 may be flexible in multiple dimensions to curve with at leastabout a curvature of average human eye ball (e.g. 25 mm in diameter). Inone embodiment, device 300 may include multiple hexagonally packedmodules with boundaries between adjacent modules perforated withperforation holes.

Each module, such as module 301, may include a group of pixel units in apartition of a device. The partition may be fabricated in a hexagonalshape, rectangular shape, or other applicable shapes. In one embodiment,perforation holes may allow fluid to exchange between different surfacesof device 300. Boundaries between adjacent modules, such as boundary 303may include metal trace (or other conductive trace or conductive lines)as signal lines for the adjacent modules to directly communicate witheach other. Metal traces may provide power distribution among themodules. Perforation can maintain some fluidic flow between tissues ofboth sides of the device (e.g. implanted within the tissues) through theperforation holes. The complete removal of integrated circuit material(e.g. silicon) between the polymer and barrier layers except metal linesalong the boundaries can increase the moldability of the device.

FIGS. 4A-4B are block diagrams illustrating cross sectional views offlexible devices in one embodiment of the present invention. Crosssection 400A of FIG. 4A may indicate a flexible integrated device havingmultiple pixel units 417, 419, 421, 425 with layered structures, such assilicon layer 407, oxide and metal interconnect layers 409 orbiocompatible layers including polymer 401 and barrier layer. Unit 417may include transistors 403, photo sensor 405 in silicon layer 407 andelectrode 413 coupled with circuitry (e.g. including transistors 403)via aluminum 411. Perforation hole 403 may be formed across the devicealong a boundary between adjacent modules. For example, units 417, 419may be grouped in one module adjacent to a separate module includingunits 421, 425.

Cross section 400B may indicate a cross sectional view between adjacentmodules (or pixel units) of a flexible integrated device with a cuttingplane across a boundary of the modules without cutting throughperforation holes. Passivated metal lines or other flexible, conductivelines, such as metal wire 423, can run across the boundary (e.g. betweenthe perforations holes) to bring electrical signals from unit to unit.

FIGS. 5A-5J are block diagrams illustrating a sequence of fabricationprocesses for flexible devices in one embodiment of the presentinvention. In one embodiment, CMOS and integration of photo sensors withelectrode arrays in structure 500A of FIG. 5A may be fabricated using astandard or slightly modified CMOS technology or a CMOS image sensor(CIS) technology on silicon wafer. Preferably, the silicon wafer maycomprise an SOI (Silicon On Insulator) wafer with a silicon epitaxiallayer a few micrometers in thickness. A PN junction diode may be usedvia the modified CMOS technology as a photo sensor. Alternatively, photosensors with optimized doping profiles and anti-reflection coatings maybe used via the CIS technology. In certain embodiments, CMOS-compatibleconducting films such as TiN might be deposited on top of electrodelayers (e.g. aluminum 511) before patterning electrodes. The electrodesmay be exposed in the final pad opening step of a conventional CMOSprocess.

In one embodiment, structure 500A of FIG. 5A may comprise layeredstructures for a flexible integrated device including transistors 505,photo sensor 507, aluminum 511 for pixel unit 513 over silicon layer (orsemiconductor layer) 503, oxide/metal layers 509, Si substrate 501 andoptional oxide layer 541. Structure 500A may include pixel units 515,517, 519 having similar components as in pixel unit 513. Structure 500Amay have a front side (or front surface, transistor side) 537 and a backside 535 opposite to the front side 537. Structure 500A may includepassivation layer 539 as a result of, for example, a CMOS process. Frontside 537 may correspond to the chip surface of a wafer or a siliconchip.

Subsequently, as shown in FIG. 5B, the front surface of a layeredstructure may be further passivated by adhesion/barrier thin films (e.g.about 0.1 μm to a few μm in thickness) based on, for example, SiC,diamond or DLC (Diamond-Like-Carbon) material or layers. In oneembodiment, structure 500B of FIG. 5B may include barrier layer 525 as aresult of the passivation. The adhesive/barrier thin films may coveralready opened pad and electrode areas for a flexible integrated device,for example, at the final step of a CMOS process.

After the passivation process, pad and electrode areas may be reopenedby photolithography and etching with a slightly smaller window sizesthan the original window sizes, which are smaller than the pad size andelectrode size made in the CMOS process. As a result, the exposed sidewalls surround the pads and electrodes may be protected by theadhesive/barrier layer deposited during the passivation process. Theexposed side walls, if not protected or covered, may expose materials ofthe standard CMOS passivation layers such as PECVD (Plasma-EnhancedChemical Vapor Deposition) silicon dioxides and silicon nitrides.

In one embodiment, a metal electrode, such as aluminum 511, may beapplicable for an electrode. A biocompatible polymer deposition, such asbiocompatible polymer (I) 523, may be applied over a barrier layer, suchas barrier layer 525. The biocompatible polymer may be based onPolyimide, PDMS (Polydimethylsiloxane), Parylene, liquid-crystal polymeror other applicable biocompatible material. In one embodiment, thebiocompatible material may be selected according to standards specifiedvia ISO 10993 standard. After applying the biocompatible layer, in oneembodiment, a first handle wafer may be bonded to the front side of thedevice wafer. For example, structure 500C may include handle substrate(I) 543 bonded via glue 545 in FIG. 5C. Structure 500C may be ready forthinning treatment from the backside. In some embodiments, electrodescan be opened right after the biocompatible polymer layer, such asbiocompatible polymer (I) 523, is deposited.

Turning now to FIG. 5D, silicon substrate of a device wafer, such assubstrate 501 of FIG. 5C, can by thinned down to a proper thickness by acombination of lapping and chemical etching steps. After bonding to thecarrier substrate, such as handle substrate (I) 543 of FIG. 5C, the Siwafer substrate, such as substrate 501, may then be mechanically thinnedto a thickness of about 50 micrometers or other proper thickness size bya wafer lapping machine. The resulting surface may include micro-crackdamages induced during the lapping process. In one embodiment, a siliconchemical etching process, such as SF6 plasma etching, dry XeF2 etching,or other applicable etching processes, may be applied to a controlledthickness to remove these damages. Alternatively, etching over asubstrate using SOI may stop at the buried oxide layer as etching stop.Typically, the thickness may be controlled to be from several microns toless than several tens of microns such that the photo sensors caneffectively absorb photons through the thickness and the substrate isstill bendable to the desirable curvature. Structure 500D of FIG. 5D mayinclude a wafer substrate which has been substantially thinned down viathe thinning process.

Turning now to FIG. 5E, adhesion/barrier thin films may be deposited ona polished and/or etched surface after the thinning process. Trenchesfor dicing lanes (or perforation holes), such as dicing lane 531 may beformed. Barrier layer 527 may be deposited over the backside ofstructure 500E of FIG. 5E. Subsequently, perforation holes (or viaholes) between device front and back surfaces may be patterned andopened by, for example, lithography and RIE (Reactive Ion Etching)processes or other applicable processes. For example, structure 500F ofFIG. 5F may include perforation hole or dicing lane 531. In someembodiment, edges of a flexible device may be similarly opened as shownin open 539 of FIG. 5F.

Turning now to FIG. 5G, a polymer layer may be further etched through toa handle substrate for perforation holes. For example, structure 500Gmay include perforation hole 531 etched through biocompatible polymer(I) 523 to handle substrate (I) 543. Subsequently, a secondbiocompatible polymer layer may be deposited and patterned to open upthe perforation holes. For example, biocompatible polymer (II) 529 maybe deposited over the backside of structure 500G and opened forperforation hole 531. Two biocompatible layers may seal together to wraparound a device as similarly shown in seal 535 of FIG. 5G. In oneembodiment, biocompatible polymer 529 (e.g. 10 μm thick) may be thickerthan barrier layer 527 (e.g. about 1 or 2 μm thick). Biocompatiblepolymers 529, 523 may be of a similar size of thickness.

Subsequently, a second handle substrate may be bonded to a device on theopposite side of a first handle substrate, which has already been bonedto the device. The first handle substrate may be removed from thedevice. For example, structure 500H of FIG. 5H may include a newlybonded handle substrate (II) 533 over the back side with the firsthandle substrate, such as handle substrate (I) 543, removed from thefront side.

After removing a handle substrate from the front surface, electrodes maybe exposed by applying lithography and RIE (Reactive Ion Etching)process or other applicable processes. For example, structure 500I ofFIG. 5I may include an opening through biocompatible polymer (I) 523 forelectrode 521 on the front side. Electrode 521 may comprise conductivemetallic material such as gold, platinum and/or copper. In oneembodiment, electrode 521 may be covered by another layer ofmetallization (IrOx, Pt, TiN, FeOx etc.) for a betterelectrode-to-electrolyte interface. Alternatively or optionally, anelectrode may include an optional dielectric layer (e.g. a thin layer ofhigh-k dielectrics of about 0.1 μm), such as dielectric 535 of FIG. 5I,for providing stimulation based on displacement current instead ofdirect current. In some embodiments, another optional adhesive layer,such as about a few micron to less than 0.1 μm of laminin, may bedeposited on the top surface of the electrode (or a flexible device) tohelp the electrode (or the flexible device) to adhere to tissues forimproving implantation. Finally, a second handle wafer may be removed tocomplete the fabrication process of a flexible integrated device. Forexample, structure 500J of FIG. 5J may represent a flexible integrateddevice without a second handle substrate, such as handle substrate (II)533 of FIG. 5I.

FIGS. 5.1A-5.1F are block diagrams illustrating an alternative orpreferred sequence of fabrication processes for flexible devices in oneembodiment of the present invention. CMOS circuits and integration ofphoto sensors with micro electrode arrays in structure 5100A of FIG.5.1A may be fabricated using a standard or slightly modified CMOS/CIStechnology or other applicable technologies on a silicon wafer. Trenchesfor dicing lanes (e.g. about 50˜100 μm wide) and optional perforationholes may be processed based on front side processing without requiringmore than one carrier handler to fabricate the flexible devices. As aresult, the manufacturing procedure may be streamlined as the thinningprocess (e.g. backside lapping) may be considered a dirty process andrestricted from sending back to certain clean fabrication processes.

In one embodiment, structure 510A may include oxide/metal layer 5105 andactive silicon layer 5107 over a silicon or SOI wafer (not shown in thefigures) according to, for example, a CMOS/CIS process. The activesilicon layer 5107 may include transistors 5123 and photo sensors 5125over silicon substrate 5129 with an optional oxide layer 5131 in betweensilicon layers 5107 and 5129. At the end of a CMOS/CIS process,structure 510A may include passivation 5101 (e.g. silicon nitride/oxide)with metal contact pads, micro electrodes opened, such as metal 5103.

Turning now to structure FIG. 5.1B, structure 510B may includeelectrodes 5109 and trenches 5127 for dicing lanes or perforation holesfor flexible devices may be fabricated from structure 510A. For example,thin metal films may be added to cover the wafer of structure 510A. Athick photo resistance material may be added by spin coating the waferon the thin metal films. Electrode 5109 may be added via electroplating(e.g. including Pt or Au material) after the thick-photoresistphotolithography processes. Subsequently, the photo resistance materialand the thin metal film may be removed. In one embodiment, electrode5109 may be about the same thickness of the desired thickness of thefinal covering polymer layer (for example, 10 μm). Additional photoresistance coating and photolithography exposure may be applied to thesurface and an RIE processes are used to etch through the passivationlayer, the silicon dioxide layers, and into the silicon substrate tocreate trench 5127. Trench 5127 may be etched through the silicon area(or active silicon layer) 5107.

Subsequently, turning now to FIG. 5.1C, structure 510C may include abarrier layer 5111 deposited over structure 510B of FIG. 5.1B. Barrierlayer 5111 may be based on DLC (diamond like carbon), SiC or otherapplicable material. Fabrication to add barrier layer after forming theelectrode 5109 may ensure protection of electrode 5109 sidewallssurrounded or enclosed by the barrier layer. Biocompatible polymer layermay then be coated to cover barrier layer 5111. For example, structure510D of FIG. 5.1D may include biocompatible polymer 5113. In oneembodiment, a polymer layer of about 20 μm thick may be applied viaspin-coat and followed by curing processes. The polymer layer may beplanarized via lapping process or reactive ion etching process to closeto the electrode thickness (for example, about 10 μm thick).

Structure 510E may include electrode conductor 5115 based on SIROF(sputtered iridium oxide film). In one embodiment, SIROF may bedeposited via sputtering iridium target in oxygen-containing plasma, andusing a lift-off process to define the electrode region. Finally, anoptional thin dielectrics layer maybe deposited on top of themicroelectrode for a voltage-mode operation of the micro electrodes.

Turning now to FIG. 5.1 E, structure 510E include structure 510D of FIG.5.1D attached to carrier wafer 5115 on the front side by a glue layer(e.g. wax) 5117. Back-side Si substrate (e.g. silicon substrate 5129 ofFIG. 5.1D) may be thinned via lapping, chemical etching processesstopping at total thickness of about 20 μm (e.g. stopping at barrierlayer 5111 or the buried oxide layer if an SOI wafer is used).Subsequently, a barrier layer may be added on top of alreadythinned-downed structure 510E followed by another biocompatible polymercoating.

For example, turning now to FIG. 5.1F, structure 510F may includebarrier layer 5119 and biocompatible polymer 5121, for example, coatedover structure 510E of FIG. 5.1E, based on back-side passivation.Structure 510F may be released from carrier wafer 5115 by dissolving theglue layer 5117. As a result, one layer of barrier layer, e.g. barrierlayer 5119, may be deposited in contact of another layer of barrierlayer, e.g. barrier layer 5111. Together with the two layers ofbiocompatible polymer, e.g. polymer 5121, 5113, they may completelycover/enclose the thin chip except in the microelectrode region.

In one embodiment, die separation (or dicing) may be applied via razorblade cutting through dicing lanes, such as over trench 5127.Alternatively or optionally, perforation holes may be created byapplying additional photolithography and plasma etching and reactive ionetching processes to remove polymer and barrier layers through trench5127. An optional adhesive layer (for example, laminin or fibronectin)maybe applied on the micro electrodes surface to promote the contact oftissue to the micro electrodes.

FIGS. 6A-6D are block diagrams illustrating exemplary layered structuresof flexible devices for different approaches to implant retinaprosthesis. In one embodiment, a flexible integrated device for retinaprosthesis can include a thin substrate to allow a portion of light topenetrate through the device (or chip) when not obstructed by metals.Thus, the monolithic chip can to be used for epi-retinal prosthesis evenwhen the photo sensors and electrodes are both fabricated on the frontside of the chip.

For example, device 600A of FIG. 6A may include photo sensor 607 andelectrode 615 fabricated on the front side (or transistor side) of thedevice. Device 600A may be implanted in an epi-retinal manner with light623 coming from the back side of the device. In one embodiment,electrodes and photo sensors of device 600A may face the side towardsretina ganglion cells 621. Device 600A may include layered structuresincluding silicon 603 having transistors/sensors 605, oxide layers 609,aluminum 613 and optional tissue glue (for example, laminin, fibronectinetc.) 617 for electrode 615, biocompatible polymer 601 wrapping thedevice and optional perforation hole 619 opened through the device.

In one embodiment, device 600A may include thin silicon substrate aboutless than 10 micrometers to allow more than a few percents of lightcoming from the back side of the device to reach the photo sensors asoptical decay length of visible light may be a few microns in silicon.Thin silicon substrate may be based on fabrication processes using SOI(silicon on insulator) wafers and thinning a silicon wafer down afterthe MOS process.

Turning now to FIG. 6B, device 600B may include similar layeredstructures as in device 600A of FIG. 6A. In one embodiment, device 600Bmay be implanted in a sub-retinal manner with light 649 coming from thefront side of the device. Electrodes and photo sensors of device 600Bmay face the side towards retina bipolar cells 625 and incoming light.

In an alternative embodiment as shown in FIG. 6C, device 600C mayinclude photo sensor 633 on the front side and electrode 637 on the backside of the device. Advantageously, electrodes in device 600C will notblock incoming light to photo sensors. In one embodiment, device 600Cmay be implanted in an epi retina manner with light 647 coming from thefront side and electrodes facing retina ganglion cells 645 on the backside. Device 600C may include layered structures having silicon 629 withtransistors/sensors 631, oxide and metal interconnect layers 627,optional tissue glue 643 for electrode 637, biocompatible polymer andbarrier layers 635 wrapping the device and perforation hole 641 acrossthe front and back surfaces of the device. Electrode 637 may be coupledwith processing circuitry including, for example, transistors circuit631, through the conducting vias, such as TSV (through silicon via) inaluminum 639.

Alternatively, in FIG. 6D, device 600D may include similar layeredstructures as in device 600C of FIG. 6C. Device 600D may be implanted ina sub-retinal manner with light 653 coming from the back side of thedevice. Electrodes of device 600D may face the side towards retinabipolar cells 651.

FIGS. 7A-7B are block diagrams illustrating guard rings to providenearby return path and confine electric flows in exemplary embodimentsof the present invention. Device 700A of FIG. 7A may include electrodesfitted with local return paths, or “guard ring” to confine electric flowfrom the electrodes. In one embodiment, device 700A may be an flexibleintegrated device with layered structures including silicon 707 havingtransistors circuit 709 and photo sensor 711, oxide layers 719,electrode 715 over aluminum 717, and biocompatible polymer layers 701,703 wrapping around the device over barrier/adhesive layer 705. Device700A may be implanted within tissue 721 in a current driving mode. Forexample, current 723 from electrode 715 may follow the lowest impedancepath. Device 700A may include guard 713 as guard ring (or local returnelectrode) to provide a local return path guiding current 723 fromundesired target directions.

Similarly in FIG. 7B, device 700B may operate in a voltage driving modewith electric field 727 from electrode 715 confined via guard 713.Device 700B may include optional dielectric 725 for electrode 715.

Preferably, electric fields or electrical currents can be confined (ormade smaller, narrower) locally close to originating electrodes throughguard rings. Thus, unwanted stimulation of neural cells other thantarget neurons of each electrode, such as stimulating the bipolar cellswithout exciting the ganglion cells, may be prevented. In a flexibleintegrated device with guard rings, the electro fields from oneelectrode may not interfere with other electro fields from separateelectrodes using guard rings.

FIG. 8 is a block diagram illustrating layered structures for flexibledevices with protruding electrodes in one embodiment of the presentinvention. For example, device 800 may comprise flexible and integratedchip with protruding electrode arrays. Device 800 may include layeredstructures having metal/dielectric layers 807, silicon with activecomponents 809, and polymer and barrier layers 811 wrapping the devicewith the polymer and barrier layers 813. Electrode 803 may be elevatedwith a protruding tip in close proximity with target neuron cell 801.Preferably, when implanted, elevated stimulus electrodes can pushthrough some of separation layers of tissues to be in closer proximityto the target locations of stimulation. Thus, the required thresholdcurrent or power to depolarize the target neurons may be reduced toenable higher number of electrodes with finer resolution (e.g. higherthan, for example, at least 250 per square millimeter).

FIG. 9 is a block diagram illustrating layered structures in flexibledevices with multi-level electrode heights in one embodiment of thepresent invention. For example, device 900 may comprise flexible andintegrated chip with arrays of electrode protruding in multi-levels.Device 900 may include layered structures having metal/dielectric layers907, silicon with active components 909, and polymer and barrier layers913 wrapping the device with the polymer and barrier layers 911.Electrodes 917, 903 may be positioned in two different levels toseparately stimulate neuron cells 901, 915.

In one embodiment, multiple-level protruding electrodes, such aselectrodes 917, 903, may differentially stimulate different strata indifferent types of neuron cells (e.g. ON type cells, OFF type cells, orother applicable types of cells). For example, multiple-level protrudingelectrodes may separately target neurons ON-pathway and OFF-pathway asretina connections between bipolar cells and ganglion cells separatedinto two different levels of strata.

FIGS. 10A-10B are schematic diagrams illustrating exemplary signalprocessing circuitry in flexible devices according to one embodiment ofthe present invention. Device 1000A of FIG. 10A may include pixel unit1005 coupled with neighboring pixel units 1001, 1003, 1007, 1009 in atwo dimensional pixel unit array. Pixel unit 1005 may be indexed by (m,n) in the two dimensional pixel unit array to receive incoming light attime t represented by I(m, n, t). Each pixel unit may exchangeinformation on received light with neighboring units (or otherapplicable pixel units).

In one embodiment, each pixel unit may include signal processingcircuitry to receive inputs from neighboring pixel units. For example,referring to FIG. 10A, signals I(m, n+1, t), I(m−1, n, t), I(m, n−1, t),and I(m+1, n, t) representing light received or sensed from neighboringpixel units 1001, 1003, 1007, 1009 may be available to pixel unit 1005.The arrangement of pixel units may be based on rectangular, hexagonal(e.g. with each pixel unit having six closes neighbor pixel units), orother applicable two dimensional or multi-dimensional array.

In certain embodiments, a flexible integrated device may include signalprocessing circuitry capable of simulating neuron network processingmechanisms similar to the center/surround antagonism receptive field ofneurons. For example, a pixel unit may generate a pixel current output(or a stimulus) proportional to the difference of the sum of centerpixel light intensity and the averaged sum of surround light intensityon its neighbors to excite proper RGC spiking. In general, a pixel unitmay use different weights to sum over inputs from local coupledneighboring pixel units, such as those closest neighbors, second closestneighbors, third closest neighbors, etc. to derive a processed signalderived from captured light for generating a stimulus.

For example, circuitry 1000B of FIG. 10B may include a processingelement 1015 generating a weighted output Id(m, n) 1017 from sensedsignal inputs 1019 separately weighted through weigh settings 1011, 1013(e.g. resistor components). In one embodiment, pixel unit 1005 of FIG.10A may include circuitry 1000B for signal processing. Four of sensedsignals I(m−1, n), I(m+1, n), I(m, n−1), I(m, n+1) 1019 (e.g. inputsfrom neighboring pixel units) may be weighted with equal weights of ¼ ofsensed signal I(m, n) via resistor components, such as R 1013 and R/41011. In some embodiments, weights may be set (e.g. dynamicallyconfigured) to about zero (e.g. equivalent to disconnecting fromcorresponding neighboring pixel units) for a majority of neighboringpixel units except for those pixel units at metering locations to reduceeffect of background absolute light intensity in a similar manner asmulti-point metering used in digital cameras. In some embodiments,signal subtraction may be applied in processing signals exchanged fromneighboring pixels units to generate stimuli based on relative intensityof incoming light instead of absolute intensity.

FIGS. 11A-11B are block diagrams illustrating operations of configuredflexible devices in one embodiment of the present invention. Forexample, flexible integrated device 1133 may be configurable to provideportions of functionality identified from neuron cells, such as retinalganglion cells 1105 and/or neural cell networks 1107, to reestablishdamaged or deteriorated vision perception. Neural cell networks 1107 mayinclude neuron cells such as horizontal cells, bipolar cells, amacrinecells or other retina cells etc. Device 1133 may include processingcircuitry 1101 coupled with micro electrode array 1103 capable ofsending stimuli to and/or sensing responses from neuron cells.

In one embodiment, device 1133 may be configurable when operating in acalibration/programming mode. Device 1133 may operate in other modessuch as a normal mode to stimulate neuron cells from incoming light toenable vision perception. In some embodiments, during acalibration/programming mode, sensor and processing circuitry 1101 mayswitch between a sensing mode and a driving mode to identify andconfigure processing characteristics (e.g. via a programmable logicarray or other applicable programmable circuitry) such that properstimuli can be generated for desired sensory output O(pi, qi) 1115 fromincoming light I(xi, yi) 1111 (e.g. generated light) when a portion ofthe neuron cells are unable to function properly (e.g. damaged, decayed,deteriorated etc.)

For example, sensor and processing circuitry 1101 may enter a sensorymode right after sending stimulus from incoming light I(xi, yi) 1111 tonormal working or relatively healthy neuron cells to produce sensoryoutput O(pi, qi) 1115. In some embodiments, light I(xi, yi) 1111 may begenerated to optically select and configure a portion (e.g. a pixel unitor a group of pixel units) of device 1133. Processing circuitry 1101 inthe sensing mode may be capable of detecting responses from the neuroncells, such as retinal ganglion cells 1105. The responses may bevoltages, waveforms or other applicable signals or spikes over a periodof time to represent sensory output O(pi, qi) 1115. Processing circuitry1101 may store information including relationship between incoming lightand the corresponding responses detected. The information may representinherent processing characteristics H(pi, qj, xi, yi) 1135 in neuroncells, for example, based on the relationship indicated by theexpression O=H*I.

Subsequently, as shown in FIG. 11B, processing circuitry 1101 may beconfigured to perform operations to make up for lost or altered visualinformation processing capabilities of neuron cells. For example,photoreceptive cells 1109 may be damaged or bleached to block neuralcell networks 1107 from processing sensed light signals. As a result,visual perception may be based on processing characteristics G′ (pi, qj,x′i, y′j) 1135 of retinal ganglion cells 1105.

In one embodiment, processing circuitry 1101 may be configured (e.g.automatically or manually) to perform operation (or transform operation)H′(x′i, y′j, xi, yj). For example, stimuli to retina ganglion cells 1105may be generated in the configured processing circuitry 1101 accordingto effective light input I′=H′*I to allow perceived output O′(pi, qj)1123 according to G′*I′ to be close to O(pi, qj) 1115. In oneembodiment, H′(x′i, y′j, xi, yj) may be programmed or configured basedon inherent processing characteristics H(pi, qj, xi, yj). Processingcircuitry 1101 may operate in a driving mode with the configuredprocessing capability. Device 1133 may operate in a normal mode ofoperation, or in a calibration mode of operation for further fine tuningor adjustment.

In one embodiment, processing circuitry may incorporate electricalsensing circuitry to enable measurement of retina neuron responsekinetics during a calibration mode, for example, when device 1133 isimplanted in an epi-retina manner. With the ability to switch the device(or chip) to electrical sensing right after electrical stimulation, theON cells and OFF cells can be identified through the response time, andthis information can be used to formulate the specific electricalstimulus from the nearby electrode when local light information issensed by photo sensors on the device.

FIG. 12 is a block diagram illustrating a system to configure flexibledevices in one embodiment of the present invention. System 1200 mayinclude configurable retinal prosthesis device 1133 with on-chipprocessing circuitry 1101 optically or wirelessly coupled with externalor remote control device 1201 to provide a control or feedback path fortuning/adjusting configurable device 1133. In one embodiment, processingcircuit 1101 and electrode array 1103 may include electrical parametersor settings which can be updated via external commands, for example, toadjust light sensitivity, stimulus intensity, or other applicableparameters to individual pixel level and achieved desired visualperception. In one embodiment, a patient may operate remote control 1201via user control 1207 based on perceived visions in visual cortex 1205.

In some embodiments, external commands 1203 may be optical commandsincluded in optical inputs 1209 which may comprise predetermined visualpatterns. Alternatively, external commands 1203 may be wirelesslytransmitted (e.g. based on EM signals or RF signals) to device 1133 viawireless transceiver. Device 1133 may include certain light sensingpixels together with special decoding circuit on chip to detect speciallight pulse pattern from optical input 1203 to enter the chip intocalibration mode for tuning/adjustment. Alternatively, the externalcommands may wirelessly cause device 1133 to enter a calibration mode orother modes of operation.

In one embodiment, each pixel or regions of pixels of device 1133 may beseparately accessed optically or wirelessly through light projection(e.g. into the eye on the implanted region). The pixel or regions can beelectrically accessed on chip to tune electrical stimulus parameters toachieve targeted effects of visual sensation. In one embodiment, testpatterns, e.g. via optical input 1209, can be projected onto theimplanted retina or directly viewed by implanted patients. The targetedvisual effects may be described to the patients for conducting manualtuning of parameters of implanted retina prosthesis chips using theexternal optical input device to allow the best approximation of thetargeted visual effects.

FIG. 13 is a flow diagram illustrating a method to configure flexibledevices in one embodiment described herein. Exemplary process 1300 maybe performed by a processing circuitry that may comprise hardware(circuitry, dedicated logic, etc.), software (such as machine codeexecuted in a machine or processing device), or a combination of both.For example, process 1300 may be performed by some components of system1200 of FIG. 12.

In one embodiment, the processing logic of process 1300 may detect lightpatterns (e.g. predetermined) from received light via photo sensors atblock 1301. The processing logic of process 1300 may decode the capturedlight to extract the light patterns optically encoded in the light. Ondetecting the light patterns, the processing logic of process 1300 maycause a device to enter a calibration mode for configuration. The devicemay comprise an array of pixel units to receive light to enableperception of a vision from the light. The pixel units may includecircuitry configurable via electrical parameters, such as detectioncircuitry for photo sensors and/or driving circuitry for electrodes.

At block 1303, in one embodiment, the processing logic of process 1300may receive light patterns to select pixel units from an array of pixelunits of a flexible integrated device. The light patterns may beassociated with known effects of visual sensation. For example, apatient implanted with the device may be aware of which visualperception to be expected, such as the shape of the image of light, therelative intensity of the image of light or other visual effects. Atblock 1305, the processing logic of process 1300 may generate stimulifrom selected pixel units to stimulate neuron cells to cause actualeffect of visual sensation similar to a normal person should experiencewith the light patterns received. In some embodiments, the lightpatterns may include selection light patterns to identify which pixelunits should be selected.

Subsequently, at block 1307, in one embodiment, the processing logic ofprocess 1300 may receive external commands to update electricalparameters of a flexible integrated device. The external commands may beoptically or wirelessly received. The processing logic of process 1300may update the electrical parameters to cause adjustment of actualeffects of visual sensation from the light patterns (or other applicableincoming light) received via the selected pixel units updated with theelectrical parameters. The captured light (e.g. the light patterns) maybe associated with known visual effects. As a result of the update, theactual effect of visual sensation may be adjusted to match the knowneffects of visual sensation to proper configure the device. In someembodiments, light patterns may be separately generated for pixelselection and for electrical or circuitry updates for the selectedpixels.

In the foregoing specification, the invention has been described withreference to specific exemplary embodiments thereof. It will be evidentthat various modifications may be made thereto without departing fromthe broader scope of the invention as set forth in the following claims.The invention is not limited to the particular forms, drawings, scales,and detailed information disclosed. The specification and drawings are,accordingly, to be regarded in an illustrative sense rather than arestrictive sense.

What is claimed is:
 1. A fabrication method for a flexible device havingan array of pixel units for retina prosthesis, comprising: forminglayered structures including the array of pixel units over a substrate,each pixel unit comprising a processing circuitry, a micro electrode anda photo sensor; forming a first set of biocompatible layers over thelayered structures; thinning down the substrate to a controlledthickness of the substrate to allow bending of the substrate to about acurvature of a retina; and forming a second set of biocompatible layersover the thinned substrate, the second set of biocompatible layers incontact with the first set of biocompatible layers around the structureto form a sealing biocompatible layers wrapping the device to allow thedevice in long-term contact with retina tissues, wherein top surfaces ofthe micro electrodes of the pixel units are exposed through thebiocompatible layers, wherein the forming the first set of biocompatiblelayers comprises depositing a barrier layer over surfaces of the layeredstructures and the substrate, wherein side walls of the layeredstructure around surfaces of the micro electrodes are covered by thebarrier layer to protect the layered structure; and depositing the firstbiocompatible polymer layer over the barrier layer, wherein thebiocompatible polymer layer adheres to the barrier layer.
 2. The methodof claim 1, wherein the barrier layer is based on thin film which isbiocompatible.
 3. The method of claim 2, wherein the thin film comprisesSiC or TiN.
 4. The method of claim 2, further comprising: covering theelectrodes with an additional metal layer to increase effectiveness ofinterface between the electrodes and electrolyte in the tissue.
 5. Themethod of claim 1, wherein the depositing of the first set ofbiocompatible layers is based on spin-coat and curing processes.
 6. Themethod of claim 5, wherein the forming of the layered structures isbased on a CMOS (Complementary metal-oxide-semiconductor) processtechnology or a CIS (CMOS Image Sensor) process technology.
 7. Themethod of claim 6, wherein the process includes a final pad opening stepand wherein the micro electrodes are exposed from the device in thefinal CMOS or CIS pad opening step.
 8. The method of claim 7, whereinthe forming of the layered structures comprises: depositing thickconducting films on top of the electrodes.
 9. The method of claim 8,further comprising: depositing a thin dielectric layer on top of themicro electrodes.
 10. The method of claim 8, further comprising:depositing an adhesive layer on top of the micro electrodes.
 11. Themethod of claim 5, wherein the substrate is made of Silicon material andwherein the thinning comprises mechanical lapping operations on thesubstrate.
 12. The method of claim 11, further comprising chemicaletching operations on the substrate to remove damages of the substrateinduced via the lapping operations.
 13. The method of claim 12, whereinthe substrate having a buried oxide layer and wherein the etchingoperations stop at the buried oxide layer.
 14. The method of claim 5,wherein the controlled thickness is measured between two opposingsurfaces of the substrate and wherein the substrate is thin enoughbetween the two opposing surfaces to allow light to reach the photosensors from either one of the two surfaces.
 15. The method of claim 14,wherein the controlled thickness is about several microns to severaltens of microns.
 16. The method of claim 5, wherein the flexible deviceis based on a CMOS device, wherein the micro electrodes comprise aconductive material, and wherein the forming the layered structurescomprises: depositing a metal seed layer over a surface of the CMOSdevice; depositing a photoresist layer for photolighrography; platingthe conductive material according to the photoligraphaphy; and strippingthe photoresist layer and metal seed layer to expose the microelectrodes.
 17. The method of claim 16, wherein the flexible device ispartitioned from the substrate according to dicing lanes includingtrenches, the method further comprising: etching out material includingoxides and silicon for the trenches based on RIE (Reactive Ion Etching)process.
 18. The method of claim 16, further comprising: covering themicro electrodes with an additional metal layer to increaseeffectiveness of interface between the micro electrodes and electrolytein the tissues.
 19. The method of claim 5, wherein the device has afront surface and a back surface, further comprising: opening up aplurality of perforation holes between the front and back surfaces toallow fluidic flow through the devices via the perforation holes,wherein each perforation hole is walled with the biocompatible layer.20. The method of claim 19, wherein the pixel units are packaged in thelayered structure with boundaries separating the units, and wherein theperforation holes are located in the boundaries.
 21. The method of claim19, wherein the perforation holes are opened between the pixel unitsperpendicular to chip surface of the device.
 22. The method of claim 1,wherein the thickness of the substrate is controlled to allow the photosensor to effectively absorb photons through the thickness of thesubstrate.
 23. The method of claim 1, wherein the substrate is based ona silicon wafer of a CMOS (Complementary Metal-Oxide-Semiconductor)process.
 24. The method of claim 23, wherein the micro electrodes areexposed with side walls covered by the barrier layer.
 25. The method ofclaim 24, wherein the thinning down the substrate comprises: performingmechanical and chemical operations on the back side of the substrate toreduce thickness of the substrate, wherein the substrate is bonded witha handler substrate on the front side to facilitate the operations. 26.The method of claim 1, further comprising: forming a plurality of guardrings for the pixel units, each guard ring surrounding an electrode toprovide a local return path for electric flow from the electrode.